Stroke is a leading cause of death and disability in the United States. Despite scientific and technological advances, there has been limited translation into clinical outcome benefits for stroke patients. Since 2013, a cohesive and integrated Stroke Trials Network has been working to develop breakthrough stroke treatments with an emphasis on rapid execution of clinical trials with sufficient sample sizes, robust enrollment, timely completion, and rigorous and uniform infrastructure across sites. This application is in response to the recent NINDS request for Regional Coordinating Stroke Centers (RCC) in the NINDS Stroke Trials Network (PAR-17-276). The Chicago Stroke Trials Consortium (CSTC) led by the RCC at Northwestern University (NU) has been an integral part of the NIH StrokeNet. In this renewal application, we expand our network to include 12 centers in the Chicago and Milwaukee metropolitan areas: Northwestern Memorial Hospital, Lurie Children's Hospital, Shirley Ryan Ability Lab, (all part of NU's McGaw Medical Center), the University of Chicago, Rush University Medical Center, Loyola University Chicago, University of Illinois at Chicago, Medical College of Wisconsin, the Hektoen Institute for Medical Research/John H. Stroger, Jr. Hospital of Cook County, Central Dupage Hospital, Northwest Community Hospital, and Edward Hines, Jr. VA Hospital. We have enlisted institutional support including agreements to utilize a federated institutional review board process (central IRB) and master trial agreements to ensure rapid implementation of future trials from each of our participating sites. The RCC aims to combine resources, diverse faculty with stroke expertise, and access to a multi-ethnic population of stroke patients spanning from children to elderly and from acute treatment to rehabilitation. The CSTC will participate in acute stroke, rehabilitation, and prevention trials, and has expertise from investigators in vascular neurology, neurosurgery, neurocritical care, neuroradiology, interventional neuroradiology, neurorehabilitation, pediatric neurology, and emergency medicine. The amassed investigators have backgrounds in all aspects of stroke research and leadership roles in many recently completed and ongoing NIH and industry-sponsored trials. The consortium has a combined geographic referral base encompassing almost 10 million people and has a history of collaboration in clinical and scientific endeavors. Drawing from the vast geographic reach of our hospitals, their resources and investigators, and substantial contributions to StrokeNet during the initial award period, the CSTC is uniquely qualified to continue to deliver a diverse stroke patient population, provide consolidated multi-disciplinary and multi-institutional expertise and leadership for StrokeNet trials, and ensure mentoring for trainees and junior faculty seeking academic careers in stroke.